Genome-wide association study of preserved ratio impaired spirometry (PRISm)

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Genome-wide association study of preserved ratio impaired spirometry (PRISm). / Higbee, Daniel H; Lirio, Alvin; Hamilton, Fergus; Granell, Raquel; Wyss, Annah B; London, Stephanie J; Bartz, Traci M; Gharib, Sina A; Cho, Michael H; Wan, Emily; Silverman, Edwin; Crapo, James D; Lominchar, Jesus V T; Hansen, Torben; Grarup, Niels; Dantoft, Thomas; Kårhus, Line; Linneberg, Allan; O'Connor, George T; Dupuis, Josée; Xu, Hanfie; De Vries, Maaike M; Hu, Xiaowei; Rich, Stephen S; Barr, R Graham; Manichaikul, Ani; Wijnant, Sara R A; Brusselle, Guy G; Lahousse, Lies; Li, Xuan; Hernández Cordero, Ana I; Obeidat, Ma'en; Sin, Don D; Harris, Sarah E; Redmond, Paul; Taylor, Adele M; Cox, Simon R; Williams, Alexander T; Shrine, Nick; John, Catherine; Guyatt, Anna L; Hall, Ian P; Davey Smith, George; Tobin, Martin D; Dodd, James W.

In: European Respiratory Journal, Vol. 63, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Higbee, DH, Lirio, A, Hamilton, F, Granell, R, Wyss, AB, London, SJ, Bartz, TM, Gharib, SA, Cho, MH, Wan, E, Silverman, E, Crapo, JD, Lominchar, JVT, Hansen, T, Grarup, N, Dantoft, T, Kårhus, L, Linneberg, A, O'Connor, GT, Dupuis, J, Xu, H, De Vries, MM, Hu, X, Rich, SS, Barr, RG, Manichaikul, A, Wijnant, SRA, Brusselle, GG, Lahousse, L, Li, X, Hernández Cordero, AI, Obeidat, M, Sin, DD, Harris, SE, Redmond, P, Taylor, AM, Cox, SR, Williams, AT, Shrine, N, John, C, Guyatt, AL, Hall, IP, Davey Smith, G, Tobin, MD & Dodd, JW 2024, 'Genome-wide association study of preserved ratio impaired spirometry (PRISm)', European Respiratory Journal, vol. 63. https://doi.org/10.1183/13993003.00337-2023

APA

Higbee, D. H., Lirio, A., Hamilton, F., Granell, R., Wyss, A. B., London, S. J., Bartz, T. M., Gharib, S. A., Cho, M. H., Wan, E., Silverman, E., Crapo, J. D., Lominchar, J. V. T., Hansen, T., Grarup, N., Dantoft, T., Kårhus, L., Linneberg, A., O'Connor, G. T., ... Dodd, J. W. (2024). Genome-wide association study of preserved ratio impaired spirometry (PRISm). European Respiratory Journal, 63. https://doi.org/10.1183/13993003.00337-2023

Vancouver

Higbee DH, Lirio A, Hamilton F, Granell R, Wyss AB, London SJ et al. Genome-wide association study of preserved ratio impaired spirometry (PRISm). European Respiratory Journal. 2024;63. https://doi.org/10.1183/13993003.00337-2023

Author

Higbee, Daniel H ; Lirio, Alvin ; Hamilton, Fergus ; Granell, Raquel ; Wyss, Annah B ; London, Stephanie J ; Bartz, Traci M ; Gharib, Sina A ; Cho, Michael H ; Wan, Emily ; Silverman, Edwin ; Crapo, James D ; Lominchar, Jesus V T ; Hansen, Torben ; Grarup, Niels ; Dantoft, Thomas ; Kårhus, Line ; Linneberg, Allan ; O'Connor, George T ; Dupuis, Josée ; Xu, Hanfie ; De Vries, Maaike M ; Hu, Xiaowei ; Rich, Stephen S ; Barr, R Graham ; Manichaikul, Ani ; Wijnant, Sara R A ; Brusselle, Guy G ; Lahousse, Lies ; Li, Xuan ; Hernández Cordero, Ana I ; Obeidat, Ma'en ; Sin, Don D ; Harris, Sarah E ; Redmond, Paul ; Taylor, Adele M ; Cox, Simon R ; Williams, Alexander T ; Shrine, Nick ; John, Catherine ; Guyatt, Anna L ; Hall, Ian P ; Davey Smith, George ; Tobin, Martin D ; Dodd, James W. / Genome-wide association study of preserved ratio impaired spirometry (PRISm). In: European Respiratory Journal. 2024 ; Vol. 63.

Bibtex

@article{c5f2890fd18347848fe3fef58a38e970,
title = "Genome-wide association study of preserved ratio impaired spirometry (PRISm)",
abstract = "BACKGROUND: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV 1) <80% predicted and FEV 1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. METHODS: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed.RESULTS: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (r g) between PRISm and spirometric COPD (r g=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (r g=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. CONCLUSION: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 ( HLX), rs62018863 ( TMEM114) and rs185937162 ( HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity. ",
keywords = "Humans, Genome-Wide Association Study, Pulmonary Disease, Chronic Obstructive/diagnosis, Diabetes Mellitus, Type 2/genetics, Lung, Forced Expiratory Volume/genetics, Spirometry, Vital Capacity",
author = "Higbee, {Daniel H} and Alvin Lirio and Fergus Hamilton and Raquel Granell and Wyss, {Annah B} and London, {Stephanie J} and Bartz, {Traci M} and Gharib, {Sina A} and Cho, {Michael H} and Emily Wan and Edwin Silverman and Crapo, {James D} and Lominchar, {Jesus V T} and Torben Hansen and Niels Grarup and Thomas Dantoft and Line K{\aa}rhus and Allan Linneberg and O'Connor, {George T} and Jos{\'e}e Dupuis and Hanfie Xu and {De Vries}, {Maaike M} and Xiaowei Hu and Rich, {Stephen S} and Barr, {R Graham} and Ani Manichaikul and Wijnant, {Sara R A} and Brusselle, {Guy G} and Lies Lahousse and Xuan Li and {Hern{\'a}ndez Cordero}, {Ana I} and Ma'en Obeidat and Sin, {Don D} and Harris, {Sarah E} and Paul Redmond and Taylor, {Adele M} and Cox, {Simon R} and Williams, {Alexander T} and Nick Shrine and Catherine John and Guyatt, {Anna L} and Hall, {Ian P} and {Davey Smith}, George and Tobin, {Martin D} and Dodd, {James W}",
note = "The content of this work is not subject to copyright. Design and branding are copyright {\textcopyright}ERS 2024.",
year = "2024",
doi = "10.1183/13993003.00337-2023",
language = "English",
volume = "63",
journal = "The European respiratory journal",
issn = "0903-1936",
publisher = "European Respiratory Society",

}

RIS

TY - JOUR

T1 - Genome-wide association study of preserved ratio impaired spirometry (PRISm)

AU - Higbee, Daniel H

AU - Lirio, Alvin

AU - Hamilton, Fergus

AU - Granell, Raquel

AU - Wyss, Annah B

AU - London, Stephanie J

AU - Bartz, Traci M

AU - Gharib, Sina A

AU - Cho, Michael H

AU - Wan, Emily

AU - Silverman, Edwin

AU - Crapo, James D

AU - Lominchar, Jesus V T

AU - Hansen, Torben

AU - Grarup, Niels

AU - Dantoft, Thomas

AU - Kårhus, Line

AU - Linneberg, Allan

AU - O'Connor, George T

AU - Dupuis, Josée

AU - Xu, Hanfie

AU - De Vries, Maaike M

AU - Hu, Xiaowei

AU - Rich, Stephen S

AU - Barr, R Graham

AU - Manichaikul, Ani

AU - Wijnant, Sara R A

AU - Brusselle, Guy G

AU - Lahousse, Lies

AU - Li, Xuan

AU - Hernández Cordero, Ana I

AU - Obeidat, Ma'en

AU - Sin, Don D

AU - Harris, Sarah E

AU - Redmond, Paul

AU - Taylor, Adele M

AU - Cox, Simon R

AU - Williams, Alexander T

AU - Shrine, Nick

AU - John, Catherine

AU - Guyatt, Anna L

AU - Hall, Ian P

AU - Davey Smith, George

AU - Tobin, Martin D

AU - Dodd, James W

N1 - The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2024.

PY - 2024

Y1 - 2024

N2 - BACKGROUND: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV 1) <80% predicted and FEV 1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. METHODS: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed.RESULTS: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (r g) between PRISm and spirometric COPD (r g=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (r g=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. CONCLUSION: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 ( HLX), rs62018863 ( TMEM114) and rs185937162 ( HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.

AB - BACKGROUND: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV 1) <80% predicted and FEV 1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. METHODS: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed.RESULTS: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (r g) between PRISm and spirometric COPD (r g=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (r g=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. CONCLUSION: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 ( HLX), rs62018863 ( TMEM114) and rs185937162 ( HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.

KW - Humans

KW - Genome-Wide Association Study

KW - Pulmonary Disease, Chronic Obstructive/diagnosis

KW - Diabetes Mellitus, Type 2/genetics

KW - Lung

KW - Forced Expiratory Volume/genetics

KW - Spirometry

KW - Vital Capacity

U2 - 10.1183/13993003.00337-2023

DO - 10.1183/13993003.00337-2023

M3 - Journal article

C2 - 38097206

VL - 63

JO - The European respiratory journal

JF - The European respiratory journal

SN - 0903-1936

ER -

ID: 379087874